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Hive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2016 A single quantifiable viral load is predictive of virological failure inHuman Immunodeficiency Virus (HIV)-infected patients on combination antiretroviral therapy: The Austrian HIV cohort study Leierer, Gisela ; Grabmeier-Pfistershammer, Katharina ; Steuer, Andrea ; Sarcletti, Mario ; Geit, Maria ; Haas, Bernhard ; Taylor, Ninon ; Kanatschnig, Manfred ; Rappold, Michaela ; Ledergerber, Bruno ; Zangerle, Robert Abstract: Background. Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods. We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measure- ment after 6 months of unmodified cART served as baseline VL for the subsequent analyses of thetime to reach single VL levels of 200, 400, and 1000 copies/mL. Roche TaqMan 2.0 was used to quantify human immunodeficiency virus-1 ribonucleic acid. Factors associated with VF were determined byCox proportional hazards models. Results. Of 1614 patients included in the study, 68, 44, and 34 experienced VF 200, 400, and 1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL 50 and VL 51-199 copies/mL predicted VF 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06-4.55 and HR = 4.21, 95% CI = 2.15-8.22, respectively). In those with VL 51-199 copies/mL, a trend for an increased risk of VF 400 and VF 1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84-5.39 and HR = 2.52, 95% CI = 0.96-6.60, respectively). Con- clusions. These findings support closer monitoring and adherence counseling for patients with asingle measurement of quantifiable VL <200 copies/mL. DOI: https://doi.org/10.1093/ofid/ofw089 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-125219 Journal Article Published Version Originally published at: Leierer, Gisela; Grabmeier-Pfistershammer, Katharina; Steuer, Andrea; Sarcletti, Mario; Geit, Maria; Haas, Bernhard; Taylor, Ninon; Kanatschnig, Manfred; Rappold, Michaela; Ledergerber, Bruno; Zangerle, Robert (2016). A single quantifiable viral load is predictive of virological failure in Human Immunode- ficiency Virus (HIV)-infected patients on combination antiretroviral therapy: The Austrian HIVcohort study. Open Forum Infectious Diseases, 3(2):ofw089. DOI: https://doi.org/10.1093/ofid/ofw089 Open Forum Infectious Diseases MAJOR ARTICLE A Single Quantifiable Viral Load Is Predictive of Virological Failure in Human Immunodeficiency Virus (HIV)-Infected Patients on Combination Antiretroviral Therapy: The Austrian HIV Cohort Study Gisela Leierer,1,2 Katharina Grabmeier-Pfistershammer,3 Andrea Steuer,4 Mario Sarcletti,1 Maria Geit,5 Bernhard Haas,6 Ninon Taylor,7 Manfred Kanatschnig,8 Michaela Rappold,1,2 Bruno Ledergerber,9 and Robert Zangerle1; for the Austrian HIV Cohort Study Group 1Department of Dermatology and Venereology, Medical University of Innsbruck, 2Austrian HIV Cohort Study, Innsbruck, 3Department of Dermatology, Medical University of Vienna, 4Otto-Wagner Hospital, Vienna, 5Department of Dermatology, General Hospital Linz, 6Department of Internal Medicine, General Hospital Graz-West, 7Department of Internal Medicine III With Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Laboratory for Immunological and Molecular Cancer Research, Paracelsus Medical University, Salzburg, and 81st Medical Department, General Hospital Klagenfurt, Austria; 9Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland Background. Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy Downloaded from (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods. We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measurement after 6 months of unmodified cART served as baseline VL for the subse- quent analyses of the time to reach single VL levels of ≥200, ≥400, and ≥1000 copies/mL. Roche TaqMan 2.0 was used to quantify fi human immunode ciency virus-1 ribonucleic acid. Factors associated with VF were determined by Cox proportional hazards models. http://ofid.oxfordjournals.org/ Results. Of 1614 patients included in the study, 68, 44, and 34 experienced VF ≥200, ≥400, and ≥1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL ≤ 50 and VL 51–199 copies/mL predicted VF ≥ 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06–4.55 and HR = 4.21, 95% CI = 2.15–8.22, respectively). In those with VL 51–199 copies/mL, a trend for an increased risk of VF ≥400 and VF ≥1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84–5.39 and HR = 2.52, 95% CI = 0.96–6.60, respectively). Conclusions. These findings support closer monitoring and adherence counseling for patients with a single measurement of quan- tifiable VL <200 copies/mL. Keywords. cART; HIV; low-level viremia; viral load; virological failure. at Zentralbibliothek on August 4, 2016 The goal of combination antiretroviral therapy (cART) is to ob- by a subsequent undetectable VL measurement, or persistent de- tain and maintain viral suppression. Although guidelines have tectable VL [4] or even virological failure (VF). Definitions of VF recommended viral loads (VLs) to be below the limit of quanti- vary between guidelines and, accordingly, some guidelines seem fication (BLQ) of clinically accessible assays [1–4], it remains un- to be more conservative, recommending lower levels of VL (>50 clear whether VLs detectable at low levels, typically below 200 copies/mL) to be reviewed due to a potential risk of rebound [1]. copies/mL, are clinically important with regard to subsequent Others defined VF as having a VL of >200 copies/mL [2– 4], and treatment failures. At the time VL reveals 51 copies/mL or one guideline sets higher thresholds for defining VF, namely VL more, it is uncertain how it will subsequently develop. It may pos- of >1000 copies/mL [5]. Despite several investigations that fo- sibly turn out to be only a viral blip, generally indicating episodes cused on consequences of persistent low-level viremia (LLV), of transiently detectable VL above 50 copies/mL [3, 5] followed which was determined by 2 or more VL measurements [6–12], studies considering 1 single VL measurement to be predictive of VF are very rare. Only 1 study observed patients with a single Received 18 January 2016; accepted 29 April 2016. quantifiable VL below 50 copies/mL to be at higher risk of re- Presented in part: 19th International Workshop on HIV Observational Databases, Catania, Italy; 7th German-Austrian AIDS Conference, Duesseldorf, Germany; 15th European AIDS Con- bound of >50 and >400 copies/mL [13]. Different commercial ference, Barcelona, Spain. techniques are able to detect VLs at low levels. It seems that Correspondence: R. Zangerle, Department of Dermatology and Venereology, Medical Univer- sity of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria ([email protected]). low-level, positive VL results appear to be more common with Open Forum Infectious Diseases® some VL assays including the Roche Cobas AmpliPrep/Cobas © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases TaqMan 2.0 [14–16]. However, this result needs to be confirmed. Society of America. This is an Open Access article distributed under the terms of the Creative fi Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ In this study, we present data from a cohort of well de ned by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any human immunodeficiency virus (HIV)-infected patients on un- medium, provided the original work is not altered or transformed in any way, and that the work fi is properly cited. For commercial re-use, please contact [email protected]. modi ed cART with standard regimens over a recent period of DOI: 10.1093/ofid/ofw089 more than 6 months in Austria. The aim of the study was to Viral Load Predicts Virological Failure • OFID • 1 evaluate the impact of LLV, measured by TaqMan 2.0 assay, and inhibitors (NRTIs) and either a non-NRTI (NNRTI) or a boost- other factors that could increase risk of VF. Virological failure ed protease inhibitor (PI/r) or an integrase inhibitor (INSTI). was defined as HIV ribonucleic acid (RNA) levels of ≥200, Individuals with other cART regimens than those mentioned ≥400, and ≥1000 copies/mL. above were excluded (N = 411). A total of 1010 patients did not have any VL measurement between 6 and 12 months PATIENTS AND METHODS after initiation of the respective cART regimen and were also ex- The Austrian HIV Cohort Study cluded. We further excluded 103 individuals who never had VL The Austrian HIV Cohort Study (AHIVCOS) is an open, multi- BLQ. In the end, 1775 patients fulfilled the inclusion criteria, center, prospective, observational cohort study of HIV-infected and their first VL measurement between 6 and 12 months
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